SCIENTIFIC STUDIES

The main conclusions from the CH studies currently available (more than 90) are shown below. The majority of these studies have been carried out with placebos and statistical significance controls (p<0.05).

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STUDI IN VITRO

On cartilaginous tissue
Studies on cultures of animal and human chondrocytes show that the presence of CH prompts them to synthesise collagen, as well as the other components of the extracellular matrix of cartilaginous tissue (proteoglycans) 7, 43, 44. This effect is produced whether the CH comes from collagen type I or type II 43. In addition, it is dose-dependent 7, 43 and is not produced with non-hydrolyzed collagen or with hydrolyzed proteins different to collagen 43.

IN VITRO STUDIES ON CHONDROCYTES

The presence of CH in cultures of bovine chondrocytes stimulates the synthesis of type II collagen tissue (p<0.01) n comparison with cultures incubated with basal medium (BM) 43. Similar results were also obtained on human chondrocytes 44.

The presence of CH COLNATUR® (COLPROPUR®)* in cultures of human chondrocytes stimulates the synthesis of proteoglycans (aggrecan) (p<0,0001) 7. This effect is dose-dependent 7.

On bone tissue
Studies on cultures of osteoblasts and osteoclasts conclude that the presence of CH stimulates the synthesis of collagen and the oestrogenic activity of the former and inhibits the restorative activity of the latter, dose-dependently 21, 54. Other studies carried out on osteoblasts and bone marrow cells show that the presence of a type I collagen matrix induces the differentiation and maturity of the osteoblasts and the uniform mineralisation of this matrix 31, 35, 36. This effect is dose-dependent 35.

On skin tissue
Studies on cultures of fibroblasts show that the presence of the collagen peptides detected in blood after ingesting CH induces cellular proliferation and the synthesis of collagen tissue and hyaluronic acid 45, 51.

(*) COLNATUR® and COLPROPUR® are registered trademarks of the same product, which are used depending on the country.

STUDIES ON BIOAVAILABILITY

Studies on bioavailability show that oral CH is very digestible 23, 24, 42, 63. After ingestion, high concentrations of peptides are found in the blood. They contain hydroxyproline, an amino acid exclusive to collagen protein, the presence of which in blood is negligible before ingestion 23, 24. The most abundant peptide detected is Pro-Hpro 24. Dr. Oesser’s study on rats revealed that if CH or proline marked with C 14 is administered, both are equally absorbed and at a high percentage, but only CH accumulate and remain in the cartilage 42. Intestinal absorption of ingested CH reaches 82%, six hours after being ingested 63 and 95% after 12 hours 42.

Study on bioavailability through radioactive markers
After 12 hours of administering an oral dose of CH marked with isotype C 14 to mice, double the amount of radioactivity accumulates in the cartilage of the animal (C) compared to the amount accumulated when only marked proline is ingested. In addition, in the cartilage (C), the radioactivity signal remained for at least 96 hours, which indicates a notable concentration and permanence of CH in this tissue. This effect is not produced in plasma (P) or in other tissues 42.

(*) COLNATUR® and COLPROPUR® are registered trademarks of the same product, which are used depending on the country.

IN VIVO STUDIES

On joints
Studies have detected the following chondroprotective effects of CH in osteoarthritis caused by a diet with excess phosphorus: it regulates the differentiation of the chondrocytes, prevents their loss and maintains their functionality, prevents the progressive thinning of the cartilage and noticeably increases the production of glycosaminoglycans 39. These effects are attributed to the action of the bioactive dipeptide Pro-Hpro 39 on the joint cartilage, the presence of which in blood is higher after ingesting CH 23, 24. This dipeptide plays an important role in maintaining the chondrocytes, preventing a diet high in phosphorus from leading to the degradation and mineralisation of cartilaginous tissue (formation of calcifications in soft tissues and bone decalcification) 39.

On bone tissue
Studies confirm that taking CH helps to increase bone mineral density (BMD) 61, 70, 71 as well as the quantity of organic matter in the bone (collagen type I and glycosaminoglycans) 41, 78. An increase in the external diameter of the cortical bone 21 and a marked improvement in fracture resistance of the femur 21, 22, 55 and the vertebrae 16 is also recorded. Other effects that can be noticed are: a decrease in bone resorption markers in blood 21, 70, and an increase in the proliferation and differentiation of osteoblasts, alone with a reduction in the differentiation of the osteoblasts and in emptying of trabeculae 21, 70. The studies conclude that the CH modulates bone formation and the mineralisation of the bone matrix 21 and it is a therapeutic agent to consider in treating osteoporosis 70.

On skin tissue
Studies indicate that taking CH stimulates regeneration and reduces signs of skin aging 32, 40, 62 generating a significant increase in the concentration of fibroblasts and the diameter and density of the dermal collagen fibres 32, as well as the hydroxyproline content 40 and type I and IV collagen 62. CH has also been proven to be beneficial in combating photoaging and helps to overcome the skin damage caused by UV-B solar radiation 56.

CLINICAL TRIALS

On joints
Studies on patients diagnosed with osteoarthritis and on individuals with joint pain associated with their physical activity show that incorporating 10 g per day of CH into the normal diet helps to reduce joint pain and the need for rescue medication, at the same time as improving the mobility and functionality of joints 4, 5, 6, 8, 12, 13, 14, 34, 38, 48, 64, 68, 72.

The ecographic study reports a 14% thickening of the escapulohumeral and femorotibial cartilage in elite sports people who took 10g of CH per day for 6 months, versus the control group that suffered a significant decrease in the thickness of the cartilage in the same period of time48.

According to a recent study, the benefits of the intake of 10g of CH are significantly higher than those obtained by the daily intake of 1.5g of glucosamine sulphate 57.

Clinical trials on joint pain in athletes
The results in the VAS pain scale show a significant reduction in joint pain in a group of 150 athletes of both sexes who take 10g of CH per day for 24 weeks, compared to the placebo group (p<0,05). The difference is even more pronounced in the subgroup with knee pain. The conclusion is that treating sports people with CH reduces joint pain and the risk of the joints deteriorating, and enhances physical performance 14.

Change of VAS in the perception of pain when walking (left) or standing (right) between the initial visit and the last visit. (The higher the number, the higher the reduction of pain).

Clinical trials on osteoarthritis on 250 patients with Kellgren stage I and III osteoarthritis
Taking 10g of CH COLNATUR® (COLPROPUR®)* daily for six months shows a significant improvement in the % of patients that have equal or higher than 30 mm of pain reduction on the VAS scale (p=0.001) (Primary objective).

The reduction of pain of the collagen group is higher than that of the placebo group in the overall population studied (13.86%), increases in the subpopulation of patients at advanced stages (19.25%) and in those whose normal diet presents a mid-low dose of animal protein (34.89%), reaching the maximum amount in the subgroup with advanced osteoarthritis and a mid-low diet of animal protein (41.59%)8.

Comparative study of the efficacy of CH compared to glucosamine (GS) in osteoarthritis of the knees
A group of 100 men and women of 40 years old with osteoarthritis was treated daily over a 13 week period with 10g of CH or 1.5g of GS (glucosamine sulphate). The results were obtained following three criteria: WOMAC Osteoarthritis Severity Index, Quadruple VAS Pain Intensity and Quality of Life Short Form (SF)-36 Questionnaire. The group treated with CH obtained better results (p<0.05) in all parameters studied. It was concluded that CH presents more clinical efficacy than GS in osteoarthritis of the knee, with significant differences in relation to improving pain, joint functionality and quality of life 57.

On bones
Taking CH regularly reduces the concentration of bone resorption markers in the urine of women with post-menopause osteoporosis 2, 3.

Clinical trial on post-menopause osteoporosis
A group of 94 women diagnosed with post-menopause osteoporosis
and with a treatment based on intramuscular calcitonin, received a daily supplement of CH or lactose (placebo) over 24 weeks. At the beginning and end of the treatment, the levels of pyridinoline and deoxypyridinoline in their urine were measured (markers of bone resorption). It was observed that in the group treated with CH the reduction in these markers was significantly higher than in the group treated with the placebo (p<0,05). The conclusion is that therapy with CH and calcitonin has a positive effect, noticeably higher than the effect of just using calcitonin.

On skin
Clinical studies show that the continuous intake of CH improves the properties of skin, increasing its degree of hydration, elasticity, smoothness and density 29, 33, 37, 53, 65, 66, 73, 74, 75, as well as decreasing the formation, and the number and size of dermal wrinkles 18, 65, 66.

Pilot clinical trial on the dermis of post-menopausal women
Taking 10g of CH COLNATUR® (COLPROPUR®)* daily for three months by healthy post-menopausal volunteers resulted in clear improvements in the total number, length, depth and surface of dermal wrinkles 18.

(*) COLNATUR® and COLPROPUR® are registered trademarks of the same product, which are used depending on the country.

CLINICAL TRIALS ON LIGAMENTS AND TENDONS

The presence of CH in human fibroblast cultures from Achilles tendons and ligaments induces these cells to significantly increase the synthesis of collagen, elastin and proteoglycans compared to the control culture. Furthermore, there is a decrease in gene expression of collagenases, enzymes that break down collagen fibres. It is concluded that the intake of CH is effective in preventing tendon and ligament injuries caused by overuse and overload of this mechanism 76.

By computer controlled extensometer, a significant increase in the extensibility of the joint of the index finger is recorded in healthy individuals who ingest CH for 6 months. The study concludes that the intake of CH improves the flexibility and firmness of the ligaments and tendons associated with the finger joints 60.

CLINICAL TRIALS ON PROTEIN INTAKE IN ADVANCED AGE

By adding a supplement of CH to the standard care applied to patients with pressure sores (from grade II to IV), the rate of healing approximately doubles in comparison with a control group that received standard care plus a placebo, as indicated by the PUSH (Pressure Ulcer Scale for Healing) values, measured 8 weeks after starting the intake, which are significantly better in the CH group 79.

In comparison with whey protein, the CH maintains muscle mass in better condition under a regulated calorie low protein diet as often happens in old age 69 and also maintains a more positive nitric balance both in regulated calorie 69 and low calorie 80 diets. These results show that a CH supplement in the diet helps to prevent complications and reduce mortality in cases of vulnerable elderly people, especially if they have to remain at rest or in the event of sarcopenia.

CLINICAL TRIAL ON FIBROMYALGIA

In vitro studies have detected alterations in the metabolism of collagen 52 and lack of intramuscular collagen 20 in the tissues of people suffering from fibromyalgia. The clinical trials confirm that ingesting CH helps to alleviate the chronic pain and characteristic symptoms of fibromyalgia 46, 58.

Results obtained in the pilot clinical trial at 90 days with 30 people suffering from fibromyalgia 46.